Reddit AMA with Frances Wiseman

On 22 May 2019, Understanding Animal Research hosted a Reddit ‘Ask Me Anything’ (AMA) with Dr Frances Wiseman from UCL to mark Dementia Awareness Week. Dr Wiseman is a senior research fellow at UCL’s Institute of Neurology and her research focuses on the early onset of dementia in people who have Down syndrome.

Reddit users were given the opportunity to ask Dr Wiseman questions about dementia, her research, and how animals play an important role in her work. Dr Wiseman was asked a range of questions which included queries about how dementia is studied in mice to how dementia can be detected, and whether or not the cause of dementia is genetic. During the hour long session, Dr Wiseman answered all questions and the AMA was up-voted 5 times.

When asked why she used mice in her research, Dr Wiseman said

“Mice are particularly important to use when we want to test the cognitive effects of changes to the brain… The main reason we use mice is because the genes on chromosome 21 are found together in the genome in “gene blocks” in mice and rats. In other species which are more evolutionary diverged from humans the genes are found all over the genome, which makes making Down syndrome models much more challenging in those species.”

Dr Wiseman was also questioned on how the mice are used and how they are looked after, to which she replied

“To study Down syndrome in mice we alter the genetics of the mice. In some cases we add an entire extra chromosome 21, or we might add in an extra copy of a group of chromosome 21 genes which we think might be the cause of a specific Down syndrome associated condition (for example early onset Alzheimer’s disease). Using these mice we can then test our hypothesis that a certain group of genes is the cause of a Down syndrome associated condition.”

“We work under UK home-office guidelines and high welfare standards are very important to ensure that our scientific research is robust and reproducible – which is important to make it useful… Mice are very social animals so we always keep them in groups as the animals become very distressed if they are on their own. The mice always have access to food and water, nesting material and a small mouse house that they can build a nest in. The mouse facility is kept at a constant temperature and humidity to keep the mice comfortable and their cages are cleaned weekly.”

Dr Wiseman also added that

“To study Down syndrome in mice we alter the genetics of the mice. In some cases we add an entire extra chromosome 21, or we might add in an extra copy of a group of chromosome 21 genes which we think might be the cause of a specific Down syndrome associated condition.”

In regards to progress that has already been made using these mice, Dr Wiseman commented that

“Our work in mice has recently shown that the extra copy of genes on chromosome 21 other than genes for amyloid precursor protein (APP) may modulate Alzheimer’s disease development in people who have Down syndrome. We have also contributed to other colleague’s research; who have shown that cellular signaling is altered in the brain in Down syndrome and that motor neurons degeneration occurs in Down syndrome. Much of this research was first undertaken in mice but then verified in human post-mortem tissue.”

On the topic of replacing mice, Dr Wiseman stated that

“We only use mice when we can’t study the research question in another system, such as human cells grown in the lab… I have also just received funding from the National Centre for 3R’s to develop fly models of Alzheimer’s disease in Down syndrome with a collaborator at UCL.”

Speaking after the AMA, Dr Wiseman remarked how “The questions were more technical than those I am generally asked at face-to-face public engagement lectures or activity days”, also adding that “It was lovely to interact with such an informed and insightful audience.”